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Cancers
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Novel Biomarkers and Therapeutic Targets for Skin Cancer
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Novel Biomarkers and Therapeutic Targets for Skin Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 12374

Special Issue Editor

Prof. Dr. Veli-Matti Kähäri

E-Mail Website
Guest Editor
Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland
Interests: skin cancer; squamous cell carcinoma; melanoma; invasion; metastasis; matrix metalloproteinase

Special Issue Information

Dear Colleagues,

The incidence of skin cancer, both melanocyte-derived melanoma and epidermal keratinocyte-derived (basal cell carcinoma and cutaneous squamous cell carcinoma), is increasing worldwide due to the aging of the population and increased recreational exposure to sunlight.

The most important risk factor for skin cancers is long-term exposure to solar ultraviolet (UV) radiation. The mutation rate of skin cancers is one of the highest among malignant tumors. This results in molecular alterations, which promote carcinogenesis, growth, progression, invasion, and metastasis of skin cancers. The prognosis of patients with metastatic skin cancers is generally poor. Therefore, there is a need for new therapeutic strategies and for biomarkers to predict the risk of aggressive behavior of skin cancers.

This Special Issue invites research articles and reviews on molecular aspects of the biology and pathology of skin cancers, with a focus on predictive and prognostic biomarkers and targeted therapies.

Prof. Dr. Veli-Matti Kähäri
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • melanoma
  • squamous cell carcinoma
  • basal cell carcinoma
  • keratinocyte
  • melanocyte
  • invasion
  • metastasis

Published Papers (5 papers)

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Research

16 pages, 4533 KiB  
Article
Super Enhancer-Regulated LINC00094 (SERLOC) Upregulates the Expression of MMP-1 and MMP-13 and Promotes Invasion of Cutaneous Squamous Cell Carcinoma
by Minna Piipponen, Pilvi Riihilä, Jaakko S. Knuutila, Markku Kallajoki, Veli-Matti Kähäri and Liisa Nissinen
Cancers 2022, 14(16), 3980; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14163980 - 17 Aug 2022
Cited by 4 | Viewed by 1700
Abstract
Long non-coding RNAs (lncRNAs) have emerged as important regulators of cancer progression. Super enhancers (SE) play a role in tumorigenesis and regulate the expression of specific lncRNAs. We examined the role of BRD3OS, also named LINC00094, in cutaneous squamous cell carcinoma [...] Read more.
Long non-coding RNAs (lncRNAs) have emerged as important regulators of cancer progression. Super enhancers (SE) play a role in tumorigenesis and regulate the expression of specific lncRNAs. We examined the role of BRD3OS, also named LINC00094, in cutaneous squamous cell carcinoma (cSCC). Elevated BRD3OS (LINC00094) expression was detected in cSCC cells, and expression was downregulated by SE inhibitors THZ1 and JQ1 and via the MEK1/ERK1/2 pathway. Increased expression of BRD3OS (LINC00094) was noted in tumor cells in cSCCs and their metastases compared to normal skin, actinic keratoses, and cSCCs in situ. Higher BRD3OS (LINC00094) expression was noted in metastatic cSCCs than in non-metastatic cSCCs. RNA-seq analysis after BRD3OS (LINC00094) knockdown revealed significantly regulated GO terms Cell-matrix adhesion, Basement membrane, Metalloendopeptidase activity, and KEGG pathway Extracellular matrix–receptor interaction. Among the top-regulated genes were MMP1, MMP10, and MMP13. Knockdown of BRD3OS (LINC00094) resulted in decreased production of MMP-1 and MMP-13 by cSCC cells, suppressed invasion of cSCC cells through collagen I, and growth of human cSCC xenografts in vivo. Based on these observations, BRD3OS (LINC00094) was named SERLOC (super enhancer and ERK1/2-Regulated Long Intergenic non-protein coding transcript Overexpressed in Carcinomas). These results reveal the role of SERLOC in cSCC invasion and identify it as a potential therapeutic target in advanced cSCC. Full article
(This article belongs to the Special Issue Novel Biomarkers and Therapeutic Targets for Skin Cancer)
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16 pages, 2018 KiB  
Article
Proliferation and Immune Response Gene Signatures Associated with Clinical Outcome to Immunotherapy and Targeted Therapy in Metastatic Cutaneous Malignant Melanoma
by Fernanda Costa Svedman, Ishani Das, Rainer Tuominen, Eva Darai Ramqvist, Veronica Höiom and Suzanne Egyhazi Brage
Cancers 2022, 14(15), 3587; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14153587 - 22 Jul 2022
Cited by 6 | Viewed by 1836
Abstract
Targeted therapy (TT), together with immune checkpoint inhibitors (ICI), has significantly improved clinical outcomes for patients with advanced cutaneous malignant melanoma (CMM) during the last decade. However, the magnitude and the duration of response vary considerably. There is still a paucity of predictive [...] Read more.
Targeted therapy (TT), together with immune checkpoint inhibitors (ICI), has significantly improved clinical outcomes for patients with advanced cutaneous malignant melanoma (CMM) during the last decade. However, the magnitude and the duration of response vary considerably. There is still a paucity of predictive biomarkers to identify patients who benefit most from treatment. To address this, we performed targeted transcriptomics of CMM tumors to identify biomarkers associated with clinical outcomes. Pre-treatment tumor samples from 28 patients with advanced CMM receiving TT (n = 13) or ICI (n = 15) were included in the study. Targeted RNA sequencing was performed using Ion AmpliSeq ™, followed by gene set enrichment analysis (GSEA) using MSigDB’s Hallmark Gene Set Collection to identify gene expression signatures correlating with treatment outcome. The GSEA demonstrated that up-regulation of allograft rejection genes, together with down-regulation of E2F and MYC targets as well as G2M checkpoint genes, significantly correlated with longer progression-free survival on ICI while IFNγ and inflammatory response genes were associated with a better clinical outcome on TT. In conclusion, we identify novel genes and their expression signatures as potential predictive biomarkers for TT and ICI in patients with metastatic CMM, paving the way for clinical use following larger validation studies. Full article
(This article belongs to the Special Issue Novel Biomarkers and Therapeutic Targets for Skin Cancer)
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17 pages, 2898 KiB  
Article
Complement Factor D Is a Novel Biomarker and Putative Therapeutic Target in Cutaneous Squamous Cell Carcinoma
by Pegah Rahmati Nezhad, Pilvi Riihilä, Jaakko S. Knuutila, Kristina Viiklepp, Sirkku Peltonen, Markku Kallajoki, Seppo Meri, Liisa Nissinen and Veli-Matti Kähäri
Cancers 2022, 14(2), 305; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14020305 - 08 Jan 2022
Cited by 6 | Viewed by 2630
Abstract
Cutaneous squamous cell carcinoma (cSCC) is the most prevalent metastatic skin cancer. Previous studies have demonstrated the autocrine role of complement components in cSCC progression. We have investigated factor D (FD), the key enzyme of the alternative complement pathway, in the development of [...] Read more.
Cutaneous squamous cell carcinoma (cSCC) is the most prevalent metastatic skin cancer. Previous studies have demonstrated the autocrine role of complement components in cSCC progression. We have investigated factor D (FD), the key enzyme of the alternative complement pathway, in the development of cSCC. RT-qPCR analysis of cSCC cell lines and normal human epidermal keratinocytes (NHEKs) demonstrated significant up-regulation of FD mRNA in cSCC cells compared to NHEKs. Western blot analysis also showed more abundant FD production by cSCC cell lines. Significantly higher FD mRNA levels were noted in cSCC tumors than in normal skin. Strong tumor cell-associated FD immunolabeling was detected in the invasive margin of human cSCC xenografts. More intense tumor cell-specific immunostaining for FD was seen in the tumor edge in primary and metastatic cSCCs, in metastases, and in recessive dystrophic epidermolysis bullosa-associated cSCCs, compared with cSCC in situ, actinic keratosis and normal skin. FD production by cSCC cells was dependent on p38 mitogen-activated protein kinase activity, and it was induced by interferon-γ and interleukin-1β. Blocking FD activity by Danicopan inhibited activation of extracellular signal-regulated kinase 1/2 and attenuated proliferation of cSCC cells. These results identify FD as a novel putative biomarker and therapeutic target for cSCC progression. Full article
(This article belongs to the Special Issue Novel Biomarkers and Therapeutic Targets for Skin Cancer)
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14 pages, 5665 KiB  
Article
A Novel and Effective Method for Human Primary Skin Melanocytes and Metastatic Melanoma Cell Isolation
by Aneta Ścieżyńska, Anna Sobiepanek, Patrycja D. Kowalska, Marta Soszyńska, Krzysztof Łuszczyński, Tomasz M. Grzywa, Natalia Krześniak, Agata Góźdź, Paweł K. Włodarski, Ryszard Galus, Tomasz Kobiela and Jacek Malejczyk
Cancers 2021, 13(24), 6244; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13246244 - 13 Dec 2021
Cited by 9 | Viewed by 3044
Abstract
The development of an effective method of melanocyte isolation and culture is necessary for basic and clinical studies concerning skin diseases, including skin pigmentation disorders and melanoma. In this paper, we describe a novel, non-enzymatic and effective method of skin melanocyte and metastatic [...] Read more.
The development of an effective method of melanocyte isolation and culture is necessary for basic and clinical studies concerning skin diseases, including skin pigmentation disorders and melanoma. In this paper, we describe a novel, non-enzymatic and effective method of skin melanocyte and metastatic melanoma cell isolation and culture (along with the spontaneous spheroid creation) from skin or lymph node explants. The method is based on the selective harvesting of melanocytes and melanoma cells emigrating from the cultured explants. Thereby, isolated cells retain their natural phenotypical features, such as expression of tyrosinase and Melan-A as well as melanin production and are not contaminated by keratinocytes and fibroblasts. Such melanocyte and melanoma cell cultures may be very useful for medical and cosmetology studies, including studies of antitumor therapies. Full article
(This article belongs to the Special Issue Novel Biomarkers and Therapeutic Targets for Skin Cancer)
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10 pages, 1279 KiB  
Article
EVI2B Is a New Prognostic Biomarker in Metastatic Melanoma with IFNgamma Associated Immune Infiltration
by Satoru Yonekura and Kosuke Ueda
Cancers 2021, 13(16), 4110; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13164110 - 15 Aug 2021
Cited by 7 | Viewed by 2221
Abstract
Background: To assess the prognostic role and the antitumor immunological relevance of ecotropic viral integration site 2B (EVI2B) in metastatic melanoma. Methods: In this study, we integrated clinical data, mRNA expression data, and the distribution and fraction of tumor infiltrating lymphocytes (TILs) using [...] Read more.
Background: To assess the prognostic role and the antitumor immunological relevance of ecotropic viral integration site 2B (EVI2B) in metastatic melanoma. Methods: In this study, we integrated clinical data, mRNA expression data, and the distribution and fraction of tumor infiltrating lymphocytes (TILs) using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets (GSE65904 and GSE19234). Results: The univariate and multivariate analyses showed that higher gene expression of EVI2B was significantly associated with longer prognoses. The EVI2B-high melanoma tissue had favorable histological parameters such as a brisk global distribution pattern and clustering structure of TILs (i.e., Banfield and Raftery index) with enriched CD8+ T cells over regulatory T cells and increased cytotoxicity scores. In addition, EVI2B expression positively correlated with IFN-γ signature genes (CXCL10, CXCL9, HLA-DRA, IDO1, IFNG, and STAT1) and other various immunomodulatory genes. Conclusion: EVI2B is a novel prognostic biomarker with IFN-γ associated immune infiltration in metastatic melanoma. Full article
(This article belongs to the Special Issue Novel Biomarkers and Therapeutic Targets for Skin Cancer)
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